Originally employed as a film critic, he was first employed as a screenwriter in films co-writing "once upon a time in the west" with Bertalano Bertaluchi. He is often compared with Alfred Hitchcock, even though the style is very different.

He is now regarded as probably the premier Italian horror director.

With his wife Daria, he had his daughters Asia Argento and Fiore Argento, both of who have stared in his films.